System that selects an optimal model combination to predict patient risks

One or more embodiments of the invention are related to the field of health care information systems and medical devices. More particularly, but not by way of limitation, one or more embodiments of the invention enable a system that selects an optimal model combination to predict patient risks.

Many risk prediction models have been developed, and continue to be developed and refined, to predict the risks of certain adverse events occurring for individual patients in a patient population. For example, a sepsis model may predict the risk that a patient develops sepsis in the next 24 hours, based on analyses of the patient's vital signs, labs, and demographics. Medical professionals may use these models to determine which patients are at greatest risk for which events, and to adjust the care of these patients accordingly. A challenge faced by health care facilities is that so many different models exist that it is impractical to use or monitor all of them simultaneously. Similarly, although multiple models may exist for predicting the future risk of the same acute illness, determining the best model for a given population without collecting an independent data set or conducting a clinical study is difficult.

Ideally each patient care team would monitor a relatively small number of risk prediction models to assess the most critical risks for patients in the patient population served by that team. Currently the only available approach for selecting risk prediction models is to iteratively experiment with different models to find those that are effective for each environment. This approach requires the additional step of monitoring patient events through time and is time consuming and is impractical when new risk prediction models are constantly being developed. There are no known systems that automatically analyze the characteristics of a target patient group to suggest an optimal combination of risk prediction models for that patient group.

For at least the limitations described above there is a need for a system that a selects an optimal model combination to predict patient risks.

One or more embodiments of the invention may enable a system that selects an optimal model combination to predict patient risks. The system may automatically compare combinations of many models to characteristics of a target patient group to determine the optimal combination for this group.

One or more embodiments of the invention may include multiple risk models, data on a target patient group, and a processor that analyzes the risk model data and the target patient group data to automatically select an optimal model combination for the target patient group. Each risk model may be associated with: an event, one or more physiological systems associated with the event, a patient type, one or more inputs, a function that maps values of the inputs to a probability of occurrence of the event for patients of the model's patient type, and training samples, each with training sample input values and a training sample output value that is the occurrence of the event for that sample. Target patient group data may include the target patient type, target patient clinical acuity, the target patient available inputs, and target patient samples with sample input values for the target patient available inputs. The processor may select an optimal model combination for the target patient group using the following steps: The multiple models may be filtered to identify a set of applicable risk models based on the target patient group data. The processor may receive (for example from an operator) a model combination cardinality (an integer greater than or equal to two) which is the desired number of models in the combination. The processor may generate all relevant combinations of the applicable risk models with the desired cardinality, and for which different models in each relevant combination have different associated physiological systems. A cost function may then be applied to each of the relevant combinations; this cost function measures differences between each combination and a theoretically optimal combination for the target patient group. The processor may then select the model combination with the lowest associated cost.

In one or more embodiments, the filter to select applicable risk models may ensure that the model inputs are included in the target patient available inputs, and that the target patient type contains the risk model patient type.

In one or more embodiments, the cost function may be a weighted sum of cost factors.

In one or more embodiments, the cost factors may include a predicted risk distribution difference factor for each model of a combination. This factor may be based on a difference between a distributional statistic of, or a statistic applied to a predicted target patient group risk distribution and a desired value of the statistic. Illustrative statistics may include for example, without limitation, a mean, a percentile, an entropy, an entropy rate, or a distribution divergence. The predicted target patient group risk distribution may be calculated by applying the model function to the target patient sample input values and dividing the result by the mean value of the training sample output values associated with the model.

In one or more embodiments the desired value of a risk distribution statistic may be the value of the statistic applied to the training set risk distribution, which is the distribution of the training sample output values divided by the mean value of these training sample output values. In one or more embodiments the mean value of the predicted risk distribution may be compared to the mean value of the training set risk distribution.

In one or more embodiments a cost factor may be based on the difference between the 99.9th percentile of the predicted target patient group risk distribution and a maximum value of a risk display range.

In one or more embodiments the cost factors may include an outputs correlation factor, which may be a correlation coefficient between the predicted target patient group risk distributions across the models in a combination.

In one or more embodiments the cost factors may include a patient type difference factor for each model in a combination, which is based on a difference between the model's patient type and the target patient group patient type.

In one or more embodiments the cost factors may include an event frequency factor for each model in a combination, which measures how frequently the model's event occurs in the target patient group data.

In one or more embodiments the cost factors may include an entropy estimate (at a relevant scale or multiscale) for each model in the combination, which may for example measure how smooth the model's predicted target patient group risk distribution is relative to the distribution of risks in the model's training set.

In one or more embodiments the cost factors may include an input distribution similarity factor that may for example compare distributions of individual features in the target patient sample input values to distributions of the same features in the model's training sample input values, for each model in the combination.

A system that a selects an optimal model combination to predict patient risks will now be described. In the following exemplary description, numerous specific details are set forth in order to provide a more thorough understanding of embodiments of the invention. It will be apparent, however, to an artisan of ordinary skill that the present invention may be practiced without incorporating all aspects of the specific details described herein. In other instances, specific features, quantities, or measurements well known to those of ordinary skill in the art have not been described in detail so as not to obscure the invention. Readers should note that although examples of the invention are set forth herein, the claims, and the full scope of any equivalents, are what define the metes and bounds of the invention.

shows an architectural diagram of illustrative elements of one or more embodiments of the invention. In an illustrative scenario, an application administrator of a health care facility or similar organizationwants to install one or more risk prediction models for a target group of patients. This target patient group may be for example the patients in a specific unit of a hospital or similar facility, or it may be a group of similar patients that are treated in various locations. The target group of patients may be identified and grouped based for example on any or all of acuity, common procedures, demographic characteristics, etc.

A databaseof risk models is available, and the organizationwants to use a combination of models from this database that best meets the needs of that target patient group. Because databasemay contain hundreds or thousands of risk models, it is impractical to evaluate or try each model individually. Instead, automated model selection systemmay be used to automatically analyze the models and the target patient group dataandto recommend an optimal model combinationfor the target patient group. Model selection systemmay run on a processor, which may be for example, without limitation, a server, a desktop computer, a laptop computer, a notebook computer, a tablet computer, a mobile device, a CPU, a GPU, a co-processor, an ASIC, or a network of any number of any of these devices. The model selection systemmay be coupled to databaseand to data generated by or obtained from target patient group. After model selection systemgenerates recommended model combination, this combination or a variation thereof may be installed in stepin a risk assessment system for target patient group. This risk assessment system may for example continually or periodically monitor patients in the target group for the risks associated with each model in the selected multi-dimensional combination.

Because the model selection system is automated, the procedure shown inmay be repeated periodically or as needed as additional data is collected on the target patient group, or as the patient mix or health conditions in the target patient group shift over time. The comparisons and cost functions described below may also be used to monitor how well the selected model combination fits the target patient group over time.

shows data associated with an illustrative risk modelin risk model database. Each risk model may predict the probability (i.e., risk) of a particular event (or the probabilities of multiple events) occurring over a specified timeframe, for example. The eventassociated with illustrative modelis the development of sepsis in a patient within the next 24 hours. Events may be associated for example with the development, change, or resolution of clinical conditions; with the need for interventions such as intubation; or with other changes in patient state such as transfer to an ICU or discharge from a hospital. A model may predict the probability of any type of event or types of events that may affect or reflect patient care or patient condition. A model may be associated with any timeframe over which the probability of event occurrence is predicted. The physiological systemsassociated with modelare the systems that are related to eventof sepsis. Each model may be associated with one or more physiological systems that are related to the model's event.

Some models may be applicable to certain patient populations or illness acuity, which may be related for example to patient demographics, patient conditions, patient treatments, or any other factors that define a group of patients. For example, some models may apply only to pediatric patients, and others may apply only to adult patients. In some situations, these patient populations may correspond to a type of care unit that treats patients of this type. A patient population for a model may be defined based on any combinations of factors such as patient age or other demographics, admitting diagnoses, acuity/illness severity, and N-dimensional distributions of laboratory measurements, vital signs, and other physiological data.

Modelis associated with a patient typeof adult patients that require intensive care, who may be treated for example in an intensive care unit. The model risk prediction for eventis therefore optimized for patients in this type of unit or with this type of acuity. The patient group type associated with a model may have any level of granularity; for example, some models may be associated with adult patients in general, while others may be associated with very specific patient groups such as patients in an Adult Cardiac Surgery unit.

Each model calculates event probabilities from a set of input data, such as patient demographic information, lab results, nursing vital signs, bedside measurements, and calculated features based on any of this information. Calculated features may be designed to enhance the representation of the change in a variable through time or may better represent information embedded in the time series of measurements, waveform shape and morphology and the signature of developing illness as represented in a combination of variables. Modelhas associated input data, which is the set of inputs used to calculate the probability of sepsis occurring in the patient. Different models may use different sets of input data. Each model also has an associated functionthat calculates the probability of the event (or events) of the model occurring from the input values. This function may for example be derived using machine learning methods applied to a training datasetwith input/output data that may be obtained from similar patient populations. For example, for model, training datasetmay be obtained by collecting input dataand output data that labels each patient based on whether that patient developed sepsis during a 24-hour period. Models may use any type or types of machine learning methods, such as for example, without limitation, regression, restricted cubic spine regression, neural networks, decision trees, bagged or boosted decision trees, and ensembles of models that use any of these methods.

Model selection systemcompares data on each model to the characteristics of the target patient groupto determine an optimal model combination. Target patient group characteristics may include informationthat is known about the target patient group prior to the model selection process. In the example shown in, it is known that the patient typeof target patient groupis Adult General Medicine. In some situations, the target patient group type may be known with great specificity, while in other situations the target group may include a mix of patient types, or the specific types of patients may be unknown. Target patient group datamay also include informationon the available inputs for this patient group, such as the clinical or demographic data that is collected for these patients. In some situations, there may also be available dataon the most common events of interest that occur in the target patient group, which may be determined for example by a review of target patient medical records or by interviewing staff.

In one or more embodiments, sample patient datamay be collected from the target patient groupover some period of time, such as a month, and this data may also be used in the model selection process. Data for illustrative patientfrom the target patient group may include for example demographic and medical history information, flow sheet entries and clinical assessments (such as Glasgow comma score), vital signsobtained for the patient over time (such as blood pressure, temperature, etc.), monitoring datafrom bedside monitoring instruments such as heart monitors, parameters and waveforms from ventilators, EEG waveforms, and lab results. This data corresponds to the available inputsthat are associated with the target patient group. This data is illustrative, and one or more embodiments may collect any types of information related to the patient's condition, identity, history, or treatment. Data from a sample set of patients from the target patient groupmay be collected over the desired time period and this datasetmay be input into the model selection system.

The model selection systemmay select an optimal model combinationbased on a set of objectives. In one or more embodiments the weight given to different objectives may be set by the user of the model selection system. Illustrative objectivesthat may be considered in one or more embodiments may include for example, without limitation: selecting models designed for patient types that are similar to the patients in the target group; selecting models that predict risks for events that are similar to the events or diagnoses observed in the target patient group; selecting models that use inputs that are similar to those that are available for the target patient group; selecting models in a combination that target different physiological systems; selecting models that generate predicted event probabilities with distributions that are similar to those of the training datasets of the models; and selecting a combination of models that generate predicted event probabilities that are uncorrelated.

Selecting models designed for patient types that are similar to patients in the target group may be achieved using prior knowledge of the clinical team and administration regarding admitting practice. It may additionally be achieved by comparing distributions of individual features in the sample patient data to distributions of the same features in the model training dataset, for example, using the Kullback-Leibler divergence, Mahalanobis distances, or other distribution distance metrics.

The selected model combinationmay be used in a patient risk assessment system that is installed to monitor patients in the target patient group.shows an illustrative displayof the output of a such a risk assessment system that may be used by the medical professionalsof the unit to monitor their patients. The selected model combinationincludes two different modelsand, so the risk assessment is two-dimensional. The event probability generated by each model is normalized to a relative risk (as described below), and the relative risk for each patient is plotted on two axesandthat correspond to the two modelsand, respectively, in model combination. In this illustrative plot, each patient is identified by a bed number, and a circle with that bed number is shown at the current risk level (on the two axes) for that patient. For example, circleshows the two-dimensional risk for the patient in bed number; the relative riskfor the cardiovascular modelin combinationis 1.6, and the relative riskfor the respiratory modelin combinationis 0.7.

Dotted circles show the recent history of the patient risk level, so that the staffcan see the evolution of each patient's risk. The size of each circle shows the total risk, which may be for example defined as the distance of the circle from the origin. For example, large circleshows that the risk for patient in bed numberis very high, and dotted circleshows that the risk for this patient is increasing.

The displayof patient risk levels is illustrative; one or more embodiments of the invention may display risks calculated by selected model combinations in any desired manner. Model combinations may be two-dimensional, as in, or they may have any number of dimensions. Displays of risk levels on more than two dimensions may use various methods to show the risk on each dimension; for example, multiple plots may be shown, or attributes such as color and size may be used to show additional dimensions. Alternatively, or in addition, axes may be the composite of multiple models that provide the desired information or improved predictions when used in combination.

shows an illustrative calculation of the relative riskfor patient #in. Associated with the modelis a function, which in this example is implemented by a neural network. One or more embodiments may use any type of function or algorithm to calculate event probabilities. In this example, the neural network function is trained on a training datasetassociated with the model. This training process may for example set the weights associated with the links between nodes; for example, the training process sets the weight of linkto value. (Other links have similar weights that are not shown.) The trained functionis then applied to the inputs associated with patient #to calculate the risk for this patient. Inputs may include the patient's demographic data, vital signs, monitoring data, and lab results. The outputs of the neural network functionmay be probabilities for the event or events predicted by the model. In this example the model is associated with a single event, and functioncalculates event probabilityfor the patient. For ease of interpretation, this event probabilitymay be converted to a relative risk (RR)by dividing it by the average probabilityfor all patients in the training dataset. The average relative risk for the training dataset is therefore normalized to 1.0.

In addition to the event probability function, other information that may be associated with a model may include one or more physiological systems associated with the model's event, and characteristics of the patient group(s) on which the model is trained.shows a partial tablewith the physiological system or systemsassociated with selected model events. Some events, such as sepsis, may be associated with multiple physiological systems.shows an illustrative classification of patient types that may be associated with models. This hierarchical classification differentiates first among intensive care patients, acute care patients, and emergency care patients. Large health care facilities in particular may create specialized unit types or patient subgroups within these broad categories, as shown. Some patient group types, such as types,, and, may be specialized for certain age groups. Others such as patient types,, and, may be specialized for certain medical specialties. Some patient types such as,,, and, may be classified based on whether they contain medical patients, surgical patients, or both. Finally, a generic patient typemay include multiple types of patients, and the specifics of the patient mix may be unknown. (In these situations with target patient groups that are a mix of different patient subpopulations, an ensemble of models that are fit to those subpopulations may provide better overall risk prediction than any of these models individually.)

Turning now to details of the model selection system,shows an overview of illustrative steps that may be performed in one or more embodiments to determine an optimal model combination for a target patient group. Some or all of these steps may be executed by a processor or processors. A set of risk modelsis input into the system, along with target patient group characteristicsand sample target patient data(as described above), and an optimal model combinationis output. In a first filtering step, modelsare compared to the target patient group data to exclude models that are unsuitable or that differ substantially from the target patient data. For example, filteringmay exclude models with a patient type that differs significantly from the target patient type. If the age group for a model is different from the target patient type age group, the model may be excluded by the filter; for example, a model for pediatric patients may be inappropriate for adult patients and vice versa. Similarly, in one or more embodiments a model may be excluded if for example it is a model for intensive care patients, but the target patient group is an acute care patients.

The filtering stepmay also filter modelsbased on a comparison of the input data available from the target unit to the inputs required by the model. If the model's inputs are not available from the target unit, the model may be excluded from consideration (unless default values can be reasonably defined for the missing inputs). A model that predicts a myocardial infarction risk based on heart monitor data may be excluded from consideration from a target unit without heart monitors, for example. After filtering, the remaining applicable modelsare considered for calculation of the optimal model combination.

Model combinations with any number of models (dimensions) may be considered for a target unit. A selectionof the combination cardinality (number of models) may be made before calculating an optimal combination with this number of models. A common choice of cardinality may be two, for example, for ease of display in a risk chart such as that shown in; however, combinations with any number of models may be considered. In one or more embodiments, multiple models may be reduced to a target dimension by calculating a composite risk score (for example via a weighted and normalized root mean square calculation). A next stepis to generate combinations of the filtered applicable modelswith the desired number of dimensions. All possible combinations may be considered; however, to improve coverage of multiple body systems, combinations with multiple models that address the same physiological systems may be excluded. For example, combinations including a model for myocardial infraction and a model for hypotension might be excluded, since both models are related to the cardiovascular system. Alternatively, an ensemble model including both such models may be considered. After eliminating model combinations that address redundant physiological systems, the remaining model combinationsare ranked to find the optimal combination.

Ranking of model combinations may use a “cost function” calculated for each model combination in step. Conceptually a cost function may quantify how far a model combination deviates from some optimal values; for example, the cost function may measure the deviation between characteristics of the model combination and characteristics of the target patient group. An illustrative cost function is described below with respect to. After calculating the cost function for each combination, the combination with the lowest cost is selected in stepas the optimal model combinationfor the target patient group.

shows illustrative counts of the number of models and combinations that may be under consideration at each step. The actual counts will depend on the specific embodiment and the characteristics of the target patient group. In this example, 2000 models are in database, but only 300 applicable models remain after filtering step. Withmodels per combination as the selected combination cardinality in step, there are 300*299/2=44850 possible combinations of thefiltered applicable models; however, many of these may duplicate physiological systems. After excluding model combinations that address the same system, 17000 model combinations (with 2 models each) remain for ranking via the cost function; the lowest cost model among these 17000 is the output of the model selection system.

shows an illustrative method to calculate a cost functionfor each model combination under consideration. The illustrative cost function may be decomposed into multiple additive factorsshown in table; these factors correspond to the objectivesdiscussed with respect to. Table shows the optimal (lowest cost) valuefor each factor, and a “distance metric”for the factor that measures the deviation of a model combination from the optimal value. Associated with each factor may be a weight, which may be set as desired in each embodiment and application of the model selection system. The cost factorsthroughof tableare illustrative; one or more embodiments may use any subset of these factors or may incorporate additional factors into a cost function.

Factormeasures the differences between the patient types of the models of the combination and the patient type of the target patient group. The metric, which is illustrated in, may be applied to each model in the combination.

Factormeasures the differences between the events associated with the models of the combination and the common events in the target patient group. The metric, which is illustrated in, may be applied to each model in the combination.

Factorsandmeasure differences between the predicted risk distribution of the target patient group and desired features of this distribution. These differences may be measured for each model in the combination. The predicted risk distribution of the target patient group for a model may be calculated for example by applying the model function to the sample patient inputs for the sample obtained from the target patient group. (In one or more embodiments risks may be normalized as described below to a “relative risk” rather than an absolute probability of event occurrence.) One or more cost factors may be calculated in any desired manner from the predicted risk distribution of the target patient group. An illustrative method of calculating a cost factor from this predicted risk distribution is to calculate a statistic from the predicted risk distribution, and to measure the difference between this statistic and some desired optimal value for the statistic in the target patient group. The desired value for the statistic may be a fixed constant value, or it may be based on applying the same statistic to the risk distribution of the model's training dataset. Illustrative statistics that may be used in cost factors may include for example, without limitation, mean, median, quartiles, percentiles, ranges, variances or standard deviations, entropies, divergences, or any other function of a distribution.

Factormeasures the differences between the mean value of the predicted distribution of relative risk for each model and the corresponding mean value of predicted relative risk for the model's training dataset. The metric, which is illustrated in, may be applied to each model in the combination.

Factormeasures the differences between the ranges of the predicted distributions (as measured for example by the 99.9th percentile values) and a desired range that effectively separates high and low risk patients. The cost factor is based on the difference between the 99.9th percentile statistic applied to the predicted risk distribution for the target group and a desired maximum value of a risk display range. For illustrative factorand associated illustrative metric, this maximum value is 6.0. The metric, which is illustrated in, may be applied to each model in the combination.

Factormeasures the difference between the observed cross-correlation of the models in a combination and an ideal value of no correlation (or negative correlation). The metric, which is illustrated in, may be applied to the pairs in the model combination.

Formulashows an illustrative calculation of a cost function from the factors. This illustrative cost function is a weighted sum of the squared distances between each factor value and the optimal value, using the distance metricsand the weights. The cost function may be calculated for each model combination in the set. The optimal model combination is then obtained in stepby minimizing the cost function over the set of model combinations.

The factors and distance metrics in tableare illustrative; one or more embodiments may use different factors and may calculate factor costs in any desired manner. Costs associated with individual factors may also be combined into a total cost function in any desired manner, including but not limited to using a weighted sum of squared distances as illustrated in formula. Additional factors may include for example, without limitation, either or both of an entropy factor and an input distribution similarity factor. An entropy factor may for example include an entropy estimate (at a relevant scale or multiscale) for each model in the combination, which measures how smooth the model estimated risks are relative to the estimated risks in the training set. An input distribution similarity factor may compare distributions of individual features in the sample patient data to distributions of the same features in the model training dataset for each model in the combination, for example, using the Kullback-Leibler divergence, Mahalanobis distances, or other distribution distance metrics.

illustrate the distance metricsfor the factors.shows selected values for an illustrative distance metricthat measures the similarity of patient types. Illustrative distances are shown between patient type(cardiovascular medicine) and selected other patient types. These values are for illustration only; one or more embodiments may measure distances between patient types with any desired values. For the embodiment shown in, the distance metric between patient typeand itself is 0 since this represents a perfect match. Patient typeis closely related to patient typesince both are patients with cardiovascular conditions, so the distance is set to 1. Patient typeis at a greater distancefrom patient typesince it is concerned with a different physiological system. Patient typeis at a higher distancefrom patient typesince it includes pediatric patients while patient typeincludes adult patients. Patient typeis at a medium distancefrom patient typesince it contains a mix of all patient types, including potentially cardiovascular patients.

shows illustrative values for an event type distance metric, which may measure for example a distance between an event associated with a model and an event in the target patient. For this illustrative metric, the “distance” between a model and a target patient group is based on the frequency of the model's event occurring in the target patient group, compared to other types of events. For a target patient group where the model's event is the target group's most common event, the distance metric is zero. As the event becomes less common in the target patient group, the distance metric increases. For example, tableshows an illustrative rank-ordered list of the most common events in the target patient group. (The events of interest here are generally those that occur after admission. For example, a care unit could have 50% sepsis diagnoses because everyone with sepsis goes there for care, but that is present on admission and would not be included in the relevant event frequency as discussed here. The events of interest represent clinical deterioration post-admission, like respiratory failure requiring intubation, bleeding leading to transfusion, or possibly septic shock requiring vasopressors.)

Since sepsisis the most common observed event in this unit, the distancebetween this target patient group and a sepsis modelis 0. For an intubation model, the event that is most closely related to intubation is COPD exacerbation. Since this event is ranked 6th in the target patient group in frequency, the distancebetween the target patient group and this model is 5 (which is the rankminus 1). In one or more embodiments the distance metric related to the model's event may be based on the absolute frequency of the event in the target patient group, rather than the relative rank. For example, if the frequency of the event among the target patients is f, an illustrative distance metric may be d (event, target group)=1/f-; this metric assigns a zero metric (lowest cost) for an event that occurs in all patients, and a very high metric as the frequency of the event in the target patient group approaches zero.